The principal investigator has developed a particularly effective and appropriate model of experimental posttraumatic epilepsy utilizing the intracerebral injection of aqueous solutions ferrous or ferric salts, the principal cations found in whole blood. The addition of iron salts or heme compounds to tissue suspension, or solutions containing unsaturated fatty acids causes generation of free radical intermediates of oxygen, O2, and peroxides. Inorganic iron salts, hematin and hemoproteins stimulate peroxidation of lipids of microsomes, as well as induce changes in thioldisulfide function. Preliminary longitudinal histopathological studies have shown that focal cerebral edema, followed by cavitary necrosis and then glial proliferation characterize the evolution of change in cerebral cortex following intracerebral iron injection. Alpha-tocopheral, an antiperoxidant, prevents peroxidative injury to sulfhydryl groups of glycolipids and glycoproteins. Indeed, preliminary experiments reported herein, utilizing pretreatment of animals with alpha-tocopherol and selenium, have shown that the development of epileptiform discharges following iron salts injection into rat brain can be prevented by such treatment. This research program will: (1) Evaluate a variety of agents for intracerebral injection, to refine the model of posttraumatic epilepsy; (2) Identify the sequence of histopathological and ultrastructural changes occurring within cerebral cortex leading to epileptogenesis; and (3) Evaluate a variety of treatments, attempting to identify agents that may be useful in the prevention of posttraumatic epilepsy in humans.